Synaptic communication in the vertebrate retina will be analyzed utilizing a pharmacological approach. Experiments will be performed in the superfused retinas of amphibians and rabbits using intracellular electrophysiological techniques. The role of amino acid neurotransmitters, both excitatory and inhibitory, in mediating the synaptic transfer of visual information will be studied. Experiments will concentrate on the analysis of the neurotransmitters of photoreceptors and bipolars, both of which may use a glutamate-like neurotransmitter, and a class of amacrine cells which may release aspartate. In the distal retina, the PI will use glutamate analogs to test his model that the synaptic receptors on each class of second-order neuron preferentially binds to a different conformation of glutamate. The pharmacology of rod and cone neurotransmission will be compared. In the proximal retina, the PI plans to determine if the OFF bipolar, like the ON bipolar, may use an excitatory amino acid neurotransmitter. In addition, the pharmacology of transient vs. sustained excitation in third order neurons will be examined to assess whether this response dichotomy reflects a duality in the excitatory amino acid receptors on these neurons. Preliminary evidence hints that a sustained, aspartate-releasing ON amacrine cell may be present in the mudpuppy and this possibility and its functional significance will be investigated. Serine has potent inhibitory actions in the proximal retina and the PI plans to evaluate whether these actions reflect a true neurotransmitter role for this amino acid. Single cell staining will be performed in conjunction with the above experiments in an attempt to correlate cell morphology with physiology and pharmacology. This research offers the possibility of selectively manipulating various visual pathways in the retina. These manipulations can be used to develop clinical protocols for diagnosing retinal malfunctions. In particular, many retinal diseases involve photoreceptor degeneration and an understanding of the action of the photoreceptor neurotransmitter may provide important insights into these diseases.